Revisiting the Association Between Vitamin D Deficiency and Active Tuberculosis: A Prospective Case-Control Study in Taiwan

Background To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D <20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13% to 22% decrease in TB incidence in vitamin D supplementation groups. Methods We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. Results We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p= 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25±8.93 ng/ml vs 24.45±8.36 ng/ml, p=0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p=0.002), lower BMI (aOR: 0.81, p<0.001), liver cirrhosis (aOR: 8.99, p=0.042), and smoking (aOR: 4.52, p=0.001) were independent risk factors for incident active TB. Conclusions VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.